The xenotropic (X-tropic) C-type virus was originally detected in New Zealand Black (NZB) mice, a strain with an inherited syndrome of autoimmunity and cancer. It is probably a common endogenous murine virus. X-tropic viruses cannot exogenously infect mouse cells but productively infect cells from many heterologous species including birds. All cells from NZB mice spontaneously release large quantities of the virus, whereas cells from other mouse strains produce the virus at less frequency and titer. Individual cells from NZB mice also differ in extent of virus production. These intracellular as well as extracellular controls of X-tropic viruses will be studied. X-tropic viruses have been isolated from developing embryos, from the pancreas during differentiation, and from normal and malignant tissues. We hope to uncover the role these viruses might play in maturation and in aging processes such as autoimmunity and cancer. Various virus isolates will be characeterized to determine if different subclasses of X-tropic viruses exist. Studies of embryogenesis shall include further assays for the presence of infectious virus in embryos and developing eggs. The effect of virus infection on embryonic development and the sensitivity of developing eggs to C-type virus infection will also be examined. Evaluation of X-tropic virus expression in the pancreas during differentiation will be continued as well as experiments examining the possible role of the virus in the immune-complex nephritis of NZB/W mice. The oncogenic potental of X-tropic virus will be assessed by infecting embryos of ducks and quails. Isolates from mouse tumors will also be studied with particular attention to the possibility of virus recombinants. Phenotypically mixed murine and avian C-type viruses will be used to examine further the mechanism and control of virus assembly, replication and transformation. We shall study the role of the serum factor associated with mouse lipoproteins which neutralize specifically X-tropic virus. By interacting with virus antigen on the cell surface, this factor may regulate X-tropic virus expression and influence normal development.